| Chimeric antigen receptor(CAR)T cell therapy is a kind of adoptive cellular imrmunotherapy.T cells collected from patients by leukocyte isolation can be activated,transducted with CAR gene,expanded in vitro,and then injected back into patients to play a role in killing tumor cells specifically.The CAR is a fusion protein comprising a signaling domain which is capable of activating T cell,and a single chain variable fragment of an antibody.Glioblastoma(GBM)is the most common primary malignant brain tumor in adults.Currently,traditional treatments include surgery,radiotherapy and chemotherapy,but recurrence is common and the median survival remains only about]5 months.Epithelial gro,wth factor receptor(EGFR)was the first molecule to be linked to oncogenesis in GBM,and associated with prognosis as well.EGFR,which is overexpressed in tumors of 40-50%of GBM patients,is low or even not expressed in normal brain tissue,making it a target for the treatment of glioblastoma.Small molecule drugs targeting EGFR have been used in colorectal cancer,non-small cell lung cancer and pancreatic cancer,but ineffective for gliomas due to problems such as drug delivery.Therefore,it is of great significance to study the effect of anti-EGFR CAR T cells for GBM.In this study,two second-generation CAR structures targeting EGFR were constructed,and then stably expressed on T cells via lentivirus infection to get CAR-T cells which can be amplified in vitro.In vitro assays using three glilblastoma cell lines with high EGFR expression were conducted for CAR-T cells activity and show that CAR-T cells can kill glioblastoma cells effectively through specific activation and large amount of cytokine secretion.A mouse orthotopic xenograft tumor model was constructed in this study,and the in vivo antitumor activity of CAR-T cells was confirmed in mouse model.This study provides a good platform for studying the effect of CAR-T cells for other tumors as well as a basis for further combined treatment. |
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